tbuckley/cabot-search huggingface dataset:
Identification of Large Airway Collapse with Symptoms Using Dynamic Chest Radiography
Authors: Fred Fyles, Amy Nuttall, Thomas FitzMaurice, Ryan Robinson, Hassan Burhan
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Identification of Large Airway Collapse with Symptoms Using Dynamic Chest Radiography." American Journal of Respiratory and Critical Care Medicine, 207(4), pp. 485–486
Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System
Authors: Scott Dryden-Peterson, Andy Kim, Arthur Y. Kim, Ellen C. Caniglia, Inga T. Lennes, Rajesh Patel, Lindsay Gainer, Lisa Dutton, Elizabeth Donahue, Rajesh T. Gandhi, Lindsey R. Baden, Ann E. Woolley
Journal: Annals of Internal Medicine (2022)

In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain.
Systematic Interrogation of Tumor Cell Resistance to Chimeric Antigen Receptor T-cell Therapy in Pancreatic Cancer
Authors: Kimberly R. Hagel, Rand Arafeh, Sydney Gang, Taylor E. Arnoff, Rebecca C. Larson, John G. Doench, Nathan D. Mathewson, Kai W. Wucherpfennig, Marcela V. Maus, William C. Hahn
Journal: Cancer Research (2022)

Chimeric antigen receptor (CAR) T-cell therapy can lead to dramatic clinical responses in B-cell malignancies. However, early clinical trials with CAR T-cell therapy in non-B-cell malignancies have been disappointing to date, suggesting that tumor-intrinsic features contribute to resistance. To investigate tumor-intrinsic modes of resistance, we performed genome scale CRISPR-Cas9 screens in mesothelin (MSLN)-expressing pancreatic cancer cells. Co-culture with MSLN-targeting CAR T cells identified both antigen-dependent and antigen-independent modes of resistance. In particular, loss of the majority of the genes involved in the pathway responsible for GPI-anchor biosynthesis and attachment abrogated the ability of CAR T cells to target pancreatic cancer cells, suggesting that disruption of this pathway may permit MSLN CAR T-cell evasion in the clinic. Antigen-independent mediators of CAR T-cell response included members of the death receptor pathway as well as genes that regulate tumor transcriptional responses, including TFAP4 and INTS12. TFAP4-mediated CAR T resistance depended on the NFκB transcription factor p65, indicating that tumor resistance to CAR T-cell therapy likely involves alterations in tumor-intrinsic states. Overall, this study uncovers multiple antigen-dependent and -independent mechanisms of CAR T-cell evasion by pancreatic cancer, paving the way for overcoming resistance in this disease that is notoriously refractory to immunotherapy.The identification and validation of key determinants of CAR T-cell response in pancreatic cancer provide insights into the landscape of tumor cell intrinsic resistance mechanisms and into approaches to improve therapeutic efficacy.
Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination
Authors: Pascal Irrgang, Juliane Gerling, Katharina Kocher, Dennis Lapuente, Philipp Steininger, Katharina Habenicht, Monika Wytopil, Stephanie Beileke, Simon Schäfer, Jahn Zhong, George Ssebyatika, Thomas Krey, Valeria Falcone, Christine Schülein, Antonia Sophia Peter, Krystelle Nganou-Makamdop, Hartmut Hengel, Jürgen Held, Christian Bogdan, Klaus Überla, Kilian Schober, Thomas H. Winkler, Matthias Tenbusch
Journal: Science Immunology (2022)

RNA vaccines are efficient preventive measures to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. High levels of neutralizing SARS-CoV-2 antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the immunoglobulin G (IgG) response mainly consists of the proinflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2–specific antibodies were increasingly composed of noninflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose, on average, from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B cell population [median of 14.4%; interquartile range (IQR) of 6.7 to 18.1%] compared with the overall memory B cell repertoire (median of 1.3%; IQR of 0.9 to 2.2%) after three immunizations. This class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Because Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest
Authors: Wenjing Wu, Wenbiao Wang, Liying Liang, Junzhe Chen, Biao Wei, Xiao-Ru Huang, Xiaoqin Wang, Xueqing Yu, Hui-Yao Lan
Journal: Molecular Therapy (2022)

Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which COVID-19 induces AKI are largely unknown, and treatment remains ineffective. Here, we report that kidney-specific overexpressing SARS-CoV-2 N gene can cause AKI, including tubular necrosis and elevated levels of serum creatinine and BUN in 8-week-old diabetic db/db mice, which become worse in those with older age (16 weeks) and underlying diabetic kidney disease (DKD). Treatment with quercetin, a purified product from traditional Chinese medicine (TCM) that shows effective treatment of COVID-19 patients, can significantly inhibit SARS-CoV-2 N protein-induced AKI in diabetic mice with or without underlying DKD. Mechanistically, quercetin can block the binding of SARS-CoV-2 N protein to Smad3, thereby inhibiting Smad3 signaling and Smad3-mediated cell death via the p16-dependent G1 cell-cycle arrest mechanism in vivo and in vitro. In conclusion, SARS-CoV-2 N protein is pathogenic and can cause severe AKI in diabetic mice, particularly in those with older age and pre-existing DKD, via the Smad3-dependent G1 cell-cycle arrest mechanism. Importantly, we identify that quercetin may be an effective TCM compound capable of inhibiting COVID-19 AKI by blocking SARS-CoV-2 N-Smad3-mediated cell death pathway.
Canalization of genome-wide transcriptional activity in Arabidopsis thaliana accessions by MET1-dependent CG methylation
Authors: Thanvi Srikant, Wei Yuan, Kenneth Wayne Berendzen, Adrián Contreras-Garrido, Hajk-Georg Drost, Rebecca Schwab, Detlef Weigel
Journal: Genome biology (2022)

Despite its conserved role on gene expression and transposable element (TE) silencing, genome-wide CG methylation differs substantially between wild Arabidopsis thaliana accessions.
Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia
Authors: Farhad Ravandi, Robert J. Kreitman, Enrico Tiacci, Leslie Andritsos, Versha Banerji, Jacqueline C. Barrientos, Seema A. Bhat, James S. Blachly, Alessandro Broccoli, Timothy Call, Dai Chihara, Claire Dearden, Judit Demeter, Sasha Dietrich, Monica Else, Narendranath Epperla, Brunangelo Falini, Francesco Forconi, Douglas E. Gladstone, Alessandro Gozzetti, Sunil Iyengar, James B. Johnston, Jeffrey Jorgensen, Gunnar Juliusson, Francesco Lauria, Gerard Lozanski, Sameer A. Parikh, Jae H. Park, Aaron Polliack, Graeme Quest, Tadeusz Robak, Kerry A. Rogers, Alan Saven, John F. Seymour, Tamar Tadmor, Martin S. Tallman, Constantine S. Tam, Philip A. Thompson, Xavier Troussard, Clive S. Zent, Thorsten Zenz, Pier Luigi Zinzani, Bernhard Wörmann, Kanti Rai, Michael Grever
Journal: Blood Cancer Journal (2022)

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.
Trends in Self-reported and Biochemically Verified Cocaine and Methamphetamine Use Among Pregnant Individuals in Northern California, 2011-2019
Authors: Kelly C. Young-Wolff, Natalie E. Slama, Varada Sarovar, Mishka Terplan, Deborah Ansley, Sara R. Adams, Stacey E. Alexeeff
Journal: JAMA Network Open (2022)

This cross-sectional study uses data from the Kaiser Permanente Northern California health care system with universal screening via self-report and urine toxicology at prenatal care entrance to examine trends in cocaine and methamphetamine use among pregnant individuals from 2011 to 2019.
Machine learning in radiology: the new frontier in interstitial lung diseases
Authors: Hayley Barnes, Stephen M Humphries, Peter M George, Deborah Assayag, Ian Glaspole, John A Mackintosh, Tamera J Corte, Marilyn Glassberg, Kerri A Johannson, Lucio Calandriello, Federico Felder, Athol Wells, Simon Walsh
Journal: The Lancet Digital Health (2022)

Challenges for the effective management of interstitial lung diseases (ILDs) include difficulties with the early detection of disease, accurate prognostication with baseline data, and accurate and precise response to therapy. The purpose of this Review is to describe the clinical and research gaps in the diagnosis and prognosis of ILD, and how machine learning can be applied to image biomarker research to close these gaps. Machine-learning algorithms can identify ILD in at-risk populations, predict the extent of lung fibrosis, correlate radiological abnormalities with lung function decline, and be used as endpoints in treatment trials, exemplifying how this technology can be used in care for people with ILD. Advances in image processing and analysis provide further opportunities to use machine learning that incorporates deep-learning-based image analysis and radiomics. Collaboration and consistency are required to develop optimal algorithms, and candidate radiological biomarkers should be validated against appropriate predictors of disease outcomes.
Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters
Authors: Peter-Martin Bruch, Sascha Dietrich, Herve Finel, Ariane Boumendil, Hildegard Greinix, Thomas Heinicke, Wolfgang Bethge, Dietrich Beelen, Christoph Schmid, Hans Martin, Luca Castagna, Christof Scheid, Kerstin Schäfer-Eckart, Jörg Bittenbring, Jürgen Finke, Henrik Sengeloev, Mael Heiblig, Jan Cornelissen, Patrice Chevallier, Mohamad Mohty, Stephen Robinson, Silvia Montoto, Peter Dreger
Journal: Leukemia (2022)
Circulating mitochondrial DNA as a biomarker of survival in rheumatoid arthritis-associated interstitial lung disease
Authors: Hee-Young Yoon, Jong Sun Park, Sang Eun Lee, Su-Jin Moon, Jin Woo Song
Journal: European Respiratory Journal (2022)

Clinically evident interstitial lung disease (ILD) occurs in 10% of patients with rheumatoid arthritis (RA) and is associated with considerable morbidity and mortality [1. RA-associated ILD (RA-ILD) has a poor prognosis with a highly variable and unpredictable clinical course [2]. Although several prognostic factors, including older age, male sex, reduced lung function, and a usual interstitial pneumonia (UIP) pattern or extensive disease on high-resolution computed tomography (HRCT) have been proposed [3], their predictive capacity may be limited by insufficient respiratory effort or interobserver variability. Circulating free mitochondrial DNA (mtDNA) is released from dying cells into the circulatory system in response to injury [4] and is associated with the pathogenesis of various conditions, including ILD [5–8]. Circulating mitochondrial DNA might be a useful prognostic biomarker in patients with rheumatoid arthritis-associated interstitial lung disease <https://bit.ly/3HFqhQM> We thank Hak-Su Kim (Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea) for the valuable comments regarding the measurement of plasma mtDNA levels, Seokchan Hong (Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea) for the confirmation of RA-ILD cases, and Jooae Choe (Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea) for radiological analysis.
Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial
Authors: Mark Ezpeleta, Kelsey Gabel, Sofia Cienfuegos, Faiza Kalam, Shuhao Lin, Vasiliki Pavlou, Zhenyuan Song, Jacob M. Haus, Sean Koppe, Shaina J. Alexandria, Lisa Tussing-Humphreys, Krista A. Varady
Journal: Cell Metabolism (2022)
An αvβ3 integrin checkpoint is critical for efficient TH2 cell cytokine polarization and potentiation of antigen-specific immunity
Authors: Aydan C. H. Szeto, Ana C. F. Ferreira, Jonathan Mannion, Paula A. Clark, Meera Sivasubramaniam, Morgan W. D. Heycock, Alastair Crisp, Helen E. Jolin, Patrycja Kozik, Martin D. Knolle, Andrew N. J. McKenzie
Journal: Nature Immunology (2022)
Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration
Authors: Sean K. Ryan, Matija Zelic, Yingnan Han, Erin Teeple, Luoman Chen, Mahdiar Sadeghi, Srinivas Shankara, Lilu Guo, Cong Li, Fabrizio Pontarelli, Elizabeth H. Jensen, Ashley L. Comer, Dinesh Kumar, Mindy Zhang, Joseph Gans, Bailin Zhang, Jonathan D. Proto, Jacqueline Saleh, James C. Dodge, Virginia Savova, Deepak Rajpal, Dimitry Ofengeim, Timothy R. Hammond
Journal: Nature Neuroscience (2022)

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found in affected brain regions, but how iron accumulation influences microglia physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived microglia grown in a tri-culture system are highly responsive to iron and susceptible to ferroptosis, an iron-dependent form of cell death. Furthermore, iron overload causes a marked shift in the microglial transcriptional state that overlaps with a transcriptomic signature found in PD postmortem brain microglia. Our data also show that this microglial response contributes to neurodegeneration, as removal of microglia from the tri-culture system substantially delayed iron-induced neurotoxicity. To elucidate the mechanisms regulating iron response in microglia, we performed a genome-wide CRISPR screen and identified novel regulators of ferroptosis, including the vesicle trafficking gene SEC24B. These data suggest a critical role for microglia iron overload and ferroptosis in neurodegeneration.
Genomic Consequences of and Demographic Response to Pervasive Hybridization Over Time in Climate-Sensitive Pikas
Authors: Deyan Ge, Zhixin Wen, Anderson Feijó, Andrey Lissovsky, Wei Zhang, Jilong Cheng, Chaochao Yan, Huishang She, Dezhi Zhang, Yalin Cheng, Liang Lu, Xinlai Wu, Danping Mu, Yubo Zhang, Lin Xia, Yanhua Qu, Alfried P Vogler, Qisen Yang
Journal: Molecular Biology and Evolution (2022)

Abstract Rare and geographically restricted species may be vulnerable to genetic effects from inbreeding depression in small populations or from genetic swamping through hybridization with common species, but a third possibility is that selective gene flow can restore fitness (genetic rescue). Climate-sensitive pikas (Ochotona spp.) of the Qinghai–Tibetan Plateau (QHTP) and its vicinity have been reduced to residual populations through the movement of climatic zones during the Pleistocene and recent anthropogenic disturbance, whereas the plateau pika (O. curzoniae) remains common. Population-level whole-genome sequencing (n = 142) of six closely related species in the subgenus Ochotona revealed several phases of ancient introgression, lineage replacement, and bidirectional introgression. The strength of gene flow was the greatest from the dominant O. curzoniae to ecologically distinct species in areas peripheral to the QHTP. Genetic analyses were consistent with environmental reconstructions of past population movements. Recurrent periods of introgression throughout the Pleistocene revealed an increase in genetic variation at first but subsequent loss of genetic variation in later phases. Enhanced dispersion of introgressed genomic regions apparently contributed to demographic recovery in three peripheral species that underwent range shifts following climate oscillations on the QHTP, although it failed to drive recovery of northeastern O. dauurica and geographically isolated O. sikimaria. Our findings highlight differences in timescale and environmental background to determine the consequence of hybridization and the unique role of the QHTP in conserving key evolutionary processes of sky island species.
A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine
Authors: Lauren A. Chang, Emily Phung, Michelle C. Crank, Kaitlyn M. Morabito, Tonya Villafana, Filip Dubovsky, Judith Falloon, Mark T. Esser, Bob C. Lin, Grace L. Chen, Barney S. Graham, Tracy J. Ruckwardt
Journal: Science Translational Medicine (2022)

There is currently no licensed vaccine for respiratory syncytial virus (RSV). Here, we assess the effect of RSV fusion protein (F) conformation on B cell responses in a post hoc comparison of samples from the DS-Cav1 [prefusion (pre-F)] and MEDI7510 [postfusion (post-F)] vaccine clinical trials. We compared the magnitude and quality of the serological and B cell responses across time points and vaccines. We measured RSV A and B neutralization, F-binding immunoglobulin G titers, and competition assays at week 0 (before vaccination) and week 4 (after vaccination) to evaluate antibody specificity and potency. To compare B cell specificity and activation, we used pre-F and post-F probes in tandem with a 17-color immunophenotyping flow cytometry panel at week 0 (before vaccination) and week 1 (after vaccination). Our data demonstrate that both DS-Cav1 and MEDI7510 vaccination robustly elicit F-specific antibodies and B cells, but DS-Cav1 elicited antibodies that more potently neutralized both RSV A and B. The superior potency was mediated by antibodies that bind antigenic sites on the apex of pre-F that are not present on post-F. In the memory (CD27
Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.2
Authors: Dwight H. Owen, Navneet Singh, Nofisat Ismaila, Elizabeth Blanchard, Paul Celano, Narjust Florez, Dharamvir Jain, Natasha B. Leighl, Hirva Mamdani, Gregory Masters, Pamela R. Moffitt, Jarushka Naidoo, Tanyanika Phillips, Gregory J. Riely, Andrew G. Robinson, Erin Schenk, Bryan J. Schneider, Lecia Sequist, David R. Spigel, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2022)

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.
Thermal‐Sinterable EGaIn Nanoparticle Inks for Highly Deformable Bioelectrode Arrays
Authors: Yan Niu, Gongwei Tian, Cuiyuan Liang, Tianchi Wang, Xu Ma, Guifen Gong, Dianpeng Qi
Journal: Advanced Healthcare Materials (2022)

Abstract Liquid metal (especially eutectic gallium indium, EGaIn) nanoparticle inks overcome the poor wettability of high surface tension EGaIn to elastomer substrates and show great potential in soft electronics. Normally, a sintering strategy is required to break the oxide shells of the EGaIn nanoparticles (EGaIn NPs) to achieve conductive paths. Herein, for the first time, thermal‐sinterable EGaIn NP inks are prepared by introducing thermal expansion microspheres (TEMs) into EGaIn NP solution. Through the mechanical pressure induced by the expansion of the heated TEMs, the printed EGaIn NPs can be sintered into electrically conductive paths to achieve highly stretchable bioelectrode arrays, which exhibit giant electromechanical performance (up to 680% strain), good cyclic stability (over 2 × 10 4 cycles), and stable conductivity after high‐speed rotation (6000 rpm). Simultaneously, the recording sites are hermetically sealed by ionic elastomer layers, ensuring the complete leakage‐free property of EGaIn and reducing the electrochemical impedance of the electrodes (891.16 Ω at 1 kHz). The bioelectrode is successfully applied to monitor dynamic electromyographic signals. The sintering strategy overcomes the disadvantages of the traditional sintering strategies, such as leakage of EGaIn, reformation of large EGaIn droplets, and low throughput, which promotes the application of EGaIn in soft electronics.
Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse
Authors: Lisa R. van der Vaart, Astrid Vollebregt, Alfredo L. Milani, Antoine L. Lagro-Janssen, Ruben G. Duijnhoven, Jan-Paul W. R. Roovers, Carl H. van der Vaart
Journal: JAMA (2022)

Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase.